Genetic counseling: Hemoglobin C
Hemoglobin C Overview of Hemoglobin and genes *Hemoglobin is the protein in blood that carries oxygen and gives blood its red color *There are hundreds of different types or variants of hemoglobin **Hemoglobin A is the most common type of hemoglobin that is made in children and adults **Hemoglobin C is one of the many hemoglobin variants *The kind of hemoglobin our body makes depends on the genes we inherit *Genes are the units of inheritance that tell our bodies how to grow and develop *Some genes tell our bodies how to make protein chains that are essential components of hemoglobin *One pair of genes, called beta globin, tells the body how to make one of the components of hemoglobin *Changes in these beta globin genes can alter the instructions and can result in different types of changes in the structure of hemoglobin *We usually get one copy of the beta globin gene from our mother and one from our father **We know that you inherited one gene that was altered and results in the variant hemoglobin C being made **The other gene produces the usual type of hemoglobin Hb A **The presence of only one altered copy of the beta globin gene almost never causes symptoms or health problems for the individual (There have been rare instances where Hb C carriers have had some eye problems) **When an individual has one altered and one unaltered copy of a gene, we say that they are carriers Potential Risks for future offspring *A carrier for Hemoglobin C is at an increased risk for having children with a genetic condition (Hb SC disease) similar to, but less severe than sickle cell anemia. *Are you familiar with sickle cell anemia? *Sickle cell anemia occurs only if a person has inherited two hemoglobin S genes, one from each parent (Hb S is another variant of the beta globin gene and is even more common than hemoglobin C) *Symptoms of sickle cell anemia include: *Increased susceptibility to frequent infections *Anemia (that is not corrected with iron supplementation) *Painful episodes caused by the blood cells blocking blood flow to body tissues *The risks to children of a carrier are dependent on whether or not the other partner carries a hemoglobin variant *The fact that you are a carrier for Hb C means that there may be potential risks to your children, but this is only possible if your partner has sickle cell trait or Hb C trait *If the father of the fetus tests positive for sickle cell trait or hemoglobin C trait there is a 25% chance that the fetus will have either hemoglobin SC disease or a mild form of anemia, a 1 in 50% chance that the fetus will be a carrier like one of the parents, and a 25% chance that the fetus will make only the usual hemoglobin (type A). Symptoms of Hemoglobin SC disease (also called Hemoglobin C disease) *Hemoglobin SC disease is milder than sickle cell disease *Sometimes the symptoms don't arise until middle or late in life *Only physical sign is an enlarged spleen in 65% of individuals with Hb SC disease *Mild (hemolytic) anemia may result, accompanied by a mild-to-moderate reduction in the red cell lifespan *Patients may have sporadic episodes of joint pain. *Continued hemolysis may produce pigmented gallstones, an unusual type of gallstone composed of the dark-colored contents of red blood cells. (The cause of pigment stones is uncertain.) *Often goes unrecognized until a serious complication which may include *blood in the urine (hematuria) *pain in the hip where part of the leg bone tissue has died (aseptic necrosis of the femoral heads) *eye problems (proliferative sickle retinopathy (PSR)) which can result in bleeding in the eye and retinal detachment *In large study in Jamaica, 1/3 with Hb SC disease had PSR at varying stages Hb C (homozygous) *mild hemolytic anemia with splenomegaly *red blood cells contain less water *less deformable and are not in circulation as long *also have a decreased oxygen affinity *may develop gallstones *no special treatment necessary Incidence of sickle cell trait and Sickle cell anemia *Sickle cell trait occurs in about 8% (or 1 in 12) African Americans *Prevalence among Hispanics whose families originated from the Caribbean, Central America, or South America is approximately 4% (or 1 in 24) *Carrier rate among 2 million screened over 4 years in California showed 6,921 nonblack infants had sickle cell trait ( .35% or approximately 1 in 300) *58 out of 2 million non black children had sickle cell disease from Calif. Newborn screen *Carrier rate in Caucasians has been reported to be 1 in 600 Frequency of hemoglobin SC disease and Hb C trait *In the US: Hemoglobin SC disease has an incidence of 0.017% less than 1 in 5000 n African Americans. *Internationally: In northern Africa, the incidence of Hb C disease is approximately 0.03%. *Hb SC disease is more common in individuals of African descent, but it also has been reported in people of Hispanic and Sicilian ancestry *Gene frequency in African Americans is about 1 in every 100 to 1 in every 50 (1-2%) *Gene frequencies are highest in Ghana and Upper Volta approaching about 1 in 7 (15%) Possible to have Hb C with other beta globin variants *Hb C and Beta Thalassemia if the Beta thal mutation is null (resulting in not functional beta chain production) *Causes similar symptoms and problems as Hb SC disease Testing *Discuss ability to do simple blood test for partner to determine if they carry a Beta globin variant or Beta thalassemia so we can clarify risks for future children (hemoglobin electrophoresis with an A2 quanitiation to identify possible beta thalassemia) *Covered by most insurance companies and can be ordered by primary care physician *Some may require preauthorization so you may want to find out if this is necessary before ordering testing *Direct mutation analysis by PCR possible but I will not discuss this because Hb electrophoresis should be sufficient http://www.hopkinsmedicine.org/dnadiagnostic/betavariants.htm (lab performs complete gene sequencing and testing of known mutations once electrophoresis has been performed) Psychosocial concerns *May be nervous and think it is more serious initially *May be a lot of information to understand at once so talk about how it will be in letter *Guilt about possibly passing on something that could cause health problems *Ethnic issues surrounding the higher prevalence among minority populations that have been oppressed in the past. Other Facts about Hb C *Hemoglobin C is composed of 2 normal alpha-chains and 2 variant beta-chains, where lysine has replaced glutamic acid at position 6 *This unstable hemoglobin is less soluble and it tends to crystallize *Intracellular crystals lead to a decrease in red cell deformability and blood that is more viscous *The spleen effectively removes these crystal-containing cells *Hemoglobin C trait is not detected by solubility testing or by a sickle cell preparation. *Heterozygotes have as much as 35% hemoglobin C References *The Metabolic and Molecular Bases of Inherited Disease (8th edition). 2001. McGraw Hill. Chapter 181 Hemoglobinopathies . Weatherall, D.J., Clegg, J.B., Higgs, D.R., Wood, W.G. *Newborn screening for sickle cell disease: 4 years of experience from California's newborn screening program. Journal of Pediatric Hematology Oncology. 18(1): 36-41. (1996). *De Caluwe, J P; Alexander, M; Bondue, H. Study of 19 heterozygote AC carriers and of 5 cases of double hemoglobinopathy SC. ACTA CLINICA BELGICA. vol. 48, no. 5 (1993): 297-306. *Rana, S R; Sekhsaria, S; Castro, O L. Hemoglobin S and C traits: contributing causes for decreased mean hematocrit in African-American children. PEDIATRICS. vol. 91, no. 4 (1993 Apr): 800-802. Web resources *www.sicklecelldisease.org -- Sickle Cell Disease Association of America *http://sickle.bwh.harvard.edu/menu_sickle.html -- basic information about hemoglobin etc Notes The information in this outline was last updated in 2002. This material has been imported fom the wikibook "Genetic counseling"[ http://en.wikibooks.org/wiki/Genetic_counseling] under the GNU Free Documentation License.